Laboratory and Basic Science Research Commons^™

Compensatory Mechanisms And T Cell Migration In Mouse Models Of Dopaminergic Loss, Kristi M. Anderson

Theses & Dissertations

Parkinson’s disease (PD) is the most common neurodegenerative movement disorder and second most common neurodegenerative disorder. PD is characterized by the selective loss of dopaminergic neurons and dopamine neurotransmitter within the substantia nigra and termini in the striatum. Progressive loss of dopaminergic neurons occurs over many years in PD, and by the time movement disorder symptoms manifest, up to 50-70% of dopaminergic neurons have been lost. Several aspects of PD pathology have been described in detail, but a better understanding of PD progression is needed to develop more efficient treatments.

Motor symptoms associated with PD do not manifest until significant …

Plasmacytoid Dendritic Cell-Mediated Humoral Autoimmunity, Stephanie M. Dorta-Estremera Ph.D.

Dissertations and Theses (Open Access)

Humoral autoimmunity is characterized by the breakdown of B cell immune tolerance to self-antigens and consequent production of pathogenic autoantibodies. Plasmacytoid dendritic cells (pDCs), a potent type I interferon (IFN-I) producer, have been linked to the pathogenesis of systemic lupus erythematosus (SLE), a prototypic systemic humoral autoimmune disease. However, the cellular events that stimulate the development of humoral autoimmunity as a result of pDC activation have not been characterized. Moreover, the B cell subset(s) responsible for the generation of autoantibodies remains to be clearly identified.

The immunization of DNA-containing amyloids into non-autoimmune mice triggers the activation of pDCs and induction …

Normal Glycolytic Enzyme Activity Is Critical For Hypoxia Inducible Factor-1a Activity And Provides Novel Targets For Inhibiting Tumor Growth, Geoffrey Grandjean Phd

Dissertations and Theses (Open Access)

Normal Glycolytic Enzyme Activity is Critical for Hypoxia Inducible Factor-1α Activity and Provides Novel Targets for Inhibiting Tumor Growth

By Geoffrey Grandjean

Advisory Professor: Garth Powis, D. Phil

Unique to proliferating cancer cells is the observation that their increased need for energy is provided by a high rate of glycolysis followed by lactic acid fermentation in a process known as the Warburg Effect, a process many times less efficient than oxidative phosphorylation employed by normal cells to satisfy a similar energy demand ^[1]. This high rate of glycolysis occurs regardless of the concentration of oxygen in the cell and …

Systematic Errors In Intro Lab Video Analysis, John Zwart, Kayt E. Frisch, Tim Martin

Faculty Work Comprehensive List

In video analysis lab experiments, students frequently find large discrepancies between results based on self-filmed videos and expected values (e.g. for g determined by a fit to projectile motion data). These differences are frequently far larger than the uncertainty calculated from their fit. Using an inexpensive point-and-shoot camera with a 4x optical zoom to record video, we investigated two possible causes of this error: the effect of placing the reference meter stick at a different object-to-camera distance and the effect of the motion of interest being in a plane not perpendicular to the camera lens. When we observed these phenomena …

Lessons From Toxicology: Developing A 21st‑Century Paradigm For Medical Research, Gill Langley, Christopher P. Austin, Anil K. Balapure, Linda S. Birnbaum, John R. Bucher, Julia Fentem, Suzanne C. Fitzpatrick, John R. Fowle Iii, Robert J. Kavlock, Hiroaki Kitano, Brett A. Lidbury, Alysson R. Muotri, Shuang-Qing Peng, Dmitry Sakharov, Troy Seidle, Thales Trez, Alexander Tonevitsky, Anja Van De Stolpe, Maurice Whelan, Catherine Willett

Experimentation Collection

Biomedical developments in the 21st century provide an unprecedented opportunity to gain a dynamic systems-level and human-specific understanding of the causes and pathophysiologies of disease. This understanding is a vital need, in view of continuing failures in health research, drug discovery, and clinical translation. The full potential of advanced approaches may not be achieved within a 20th-century conceptual framework dominated by animal models. Novel technologies are being integrated into environmental health research and are also applicable to disease research, but these advances need a new medical research and drug discovery paradigm to gain maximal benefits. We suggest a new conceptual …

Steroid Receptor Isoform Expression In Drosophila Nociceptor Neurons Is Required For Normal Dendritic Arbor And Sensitivity, Aidan L. Mcparland, Taylor L. Follansbee, Gwendolyn D. Vesenka, Alexandra E. Panaitiu, Geoffrey K. Ganter

Biology Student Publications

Steroid hormones organize many aspects of development, including that of the nervous system. Steroids also play neuromodulatory and other activational roles, including regulation of sensitivity to painful stimuli in mammals. In Drosophila, ecdysteroids are the only steroid hormones, and therefore the fly represents a simplified model system in which to explore mechanisms of steroid neuromodulation of nociception. In this report, we present evidence that ecdysteroids, acting through two isoforms of their nuclear ecdysone receptor (EcR), modulate sensitivity to noxious thermal and mechanical stimuli in the fly larva. We show that EcRA and EcRB1 are expressed by third instar larvae in …

The Generation, Exploitation And Future Of Induced Pluripotent Stem Cells, Jacob Steenwyk

Scholarly Undergraduate Research Journal at Clark (SURJ)

The foundational advancements of John Gurdon and Shinya Yamanaka have improved understanding of dedifferen- tiation of cells to a pluripotent state. The seminal discovery established a novel system to study disease pathogenesis, drug screening, and toxicity, as well as sprouted the new field of regenerative medicine. In this article, the method- ology to obtain dedifferentiated cells, known as induced pluripotent stem (iPS) cells, subsequent validation, and application of which are reviewed. The experiments investigated here aim to demonstrate the capacity of iPS cells to replace the ethically-gray human embryonic cells by developing human livers and viable, healthy animals. It is …

Heterogeneous Oxidation Of Catechol, Elizabeth A. Pillar, Ruixin Zhou, Marcelo I. Guzman

Chemistry Faculty Publications

Natural and anthropogenic emissions of aromatic hydrocarbons from biomass burning, agro-industrial settings, and fossil fuel combustion contribute precursors to secondary aerosol formation (SOA). How these compounds are processed under humid tropospheric conditions is the focus of current attention to understand their environmental fate. This work shows how catechol thin films, a model for oxygenated aromatic hydrocarbons present in biomass burning and combustion aerosols, undergo heterogeneous oxidation at the air–solid interface under variable relative humidity (RH = 0–90%). The maximum reactive uptake coefficient of O₃(g) by catechol γ_O3 = (7.49 ± 0.35) × 10^–6 occurs for …

Clinical Significance Of The Integrin Α6Β4 In Human Malignancies, Rachel L Stewart, Kathleen L O'Connor

Pathology and Laboratory Medicine Faculty Publications

Integrin α6β4 is a cellular adhesion molecule that binds to laminins in the extracellular matrix and nucleates the formation of hemidesmosomes. During carcinoma progression, integrin α6β4 is released from hemidesmosomes, where it can then signal to facilitate multiple aspects of tumor progression including sustaining proliferative signaling, tumor invasion and metastasis, evasion of apoptosis, and stimulation of angiogenesis. The integrin achieves these ends by cooperating with growth factor receptors including EGFR, ErbB-2, and c-Met to amplify downstream pathways such as PI3K, AKT, MAPK, and the Rho family small GTPases. Furthermore, it dramatically alters the transcriptome …

Fabrication Of Multianalyte Ceo2 Nanograin Electrolyte–Insulator–Semiconductor Biosensors By Using Cf4 Plasma Treatment, Chyuan Haur Kao, Hsiang Chen, Fang Yao Stephen Hou, Shan Wei Chang, Che Wei Chang, Chao Sung Lai, Chin Pang Chen, Yun Yang He, Shang-Ren Lin, Kun Min Hsieh, Min Han Lin

Clinical Lab Sciences Faculty Research and Publications

Multianalyte CeO₂ biosensors have been demonstrated to detect pH, glucose, and urine concentrations. To enhance the multianalyte sensing capability of these biosensors, CF₄ plasma treatment was applied to create nanograin structures on the CeO₂ membrane surface and thereby increase the contact surface area. Multiple material analyses indicated that crystallization or grainization caused by the incorporation of flourine atoms during plasma treatment might be related to the formation of the nanograins. Because of the changes in surface morphology and crystalline structures, the multianalyte sensing performance was considerably enhanced. Multianalyte CeO₂ nanograin electrolyte–insulator–semiconductor biosensors exhibit potential for use …

An Analysis Of The Interaction Of Methylphenidate And Nicotine In Adolescent Rats: Effects On Bdnf, Elizabeth D. Freeman

Electronic Theses and Dissertations

This investigation was an analysis of the interaction of adolescent exposure to methylphenidate (MPH; trade name: Ritalin) on nicotine sensitization and conditioned place preference (CPP) in a rodent model and underlying mechanisms of this effect. Animals were treated IP with 1 mg/kg MPH or saline using a ―school day‖ regimen of five days on, two days off, from postnatal day (P) 28-50. During the final two weeks of MPH treatment, animals were either behaviorally sensitized to nicotine (0.5 mg/kg free base) or saline for 10 days, or conditioned to nicotine or saline using the CPP behavioral paradigm. In addition, three …

The Multifactorial Role Of The 3rs In Shifting The Harm-Benefit Analysis In Animal Models Of Disease, Melanie L. Graham, Mark J. Prescott

Biomedical Research and Alternative Methods Collection

Ethics on animal use in science in Western society is based on utilitarianism, weighing the harms and benefits to the animals involved against those of the intended human beneficiaries. The 3Rs concept (Replacement, Reduction, Refinement) is both a robust framework for minimizing animal use and suffering (addressing the harms to animals) and a means of supporting high quality science and translation (addressing the benefits). The ambiguity of basic research performed early in the research continuum can sometimes make harm-benefit analysis more difficult since anticipated benefit is often an incremental contribution to a field of knowledge. On the other hand, benefit …

The Effects Of Sustained, High-Velocity Exercise On Gene Expression In California Yellowtail (Seriola Lalandi), Kelli Hatter

Undergraduate Honors Theses

California Yellowtail muscle fibers have been observed to exhibit two drastically different development patterns resulting from the speeds at which they are exercised. When fish are exercised at a moderate rate their epaxial fast-twitch muscle fibers grow in diameter—hypertrophy; when they are exercised at a fast speed, more new epaxial fast-twitch muscle fibers are produced—hyperplasia. To determine the underlying reason for this difference in muscle development, my summer research project and honors thesis exercised fish at: fast, moderate, and control speeds for a sustained amount of time to determine what is happening on a cellular level to cause the observed …

Transcriptional Regulation By Dax-1 In Pluripotent And Differentiated Cells, Alexandra C. Maramba

Master's Theses

DAX-1, an orphan nuclear hormone receptor, acts mainly as a repressor through transcriptional protein complexes. Its unique structure and specific expression raises questions as to what its precise interactions are and how it mediates its repressive function. While it is known to play a role in sexual development and adrenal insufficiency, expression in certain types of cancer suggests additional functions and interactions. Knock in of DAX-1 into a low-DAX-1 expressing cancer cell line has been previously observed to increase apoptosis, while, inversely, down in a high-DAX-1 expressing cancer cell line shows a decrease in apoptosis. Target genes that belong to …

Structural And Functional Interactions Between Bro1 Domain Of Human Alix Protein And Nucleocapsid Packaging Rna Complex From Hiv, Scott Gross

Graduate School of Biomedical Sciences Theses and Dissertations

A virus is only as powerful as its ability to spread. Enveloped retroviruses, namely HIV-1, use exocytosis pathways that normal host cells use to release particles from the plasma membrane. The main pathways of interest in this study are the Endosomal Sorting Complex Required for Transport (ESCRT) and adjacent ALIX pathways. The ESCRT pathway is especially important for degradation of receptor/cargo complexes that form Multi-Vesicular Bodies (MVBs). Currently, there is no known therapy that targets this endosomal pathway, which would prevent the spread of the virus to other cells. The virus has adapted to jump from pathway to pathway when …

Age-Dependent Breakdown Of The Blood Brain Barrier And Associated Changes In S100b Ko Mice, Eric V. Brown

Graduate School of Biomedical Sciences Theses and Dissertations

Autoantibodies play an important role in many autoimmune diseases. Recent research has shown that breakdown of the blood brain barrier (BBB) occurs concomitant to generation of brain reactive autoantibodies in many neurodegenerative diseases, which serve as biomarkers and drivers of pathology. SI00B, a calcium binding protein found most highly expressed in astrocytes which ensheathe the BBB, has many functions in neural development and signaling. Currently literature indicates that S100B KO mice develop normally, with no phenotypic abnormalities. Here, it is demonstrated that S100B KO mice seem to develop a chronic BBB breakdown similar to that seen in human neurodegenerative diseases. …

Investigating Potential Therapies To Decrease The Rate Of Cystine Stone Growth In Slc3a1-/- Mice, Sruthi Damodar

Dissertations, Masters Theses, Capstones, and Culminating Projects

Cystinuria is an autosomal recessive disorder characterized by a defective renal transporter involved in the reabsorption of cystine and other dibasic amino acids. This leads to an accumulation of cystine in the urine, resulting in cystine stones. The SLC3A1/SLC7A9 cystine transporter accounts for 90% of cystine reabsorption and mutations in this transporter result in the formation of cystine stones. For this study, micro-computed tomography (µCT) scanning was evaluated for its feasibility to track accurate volumetric measurements of in vivo cystine stone growth in the Slc3a1-/- cystinuric mouse model. Six pharmacological interventions – sulforaphane, methyl selenocysteine, homocysteine, tiopronin, TPEN and a …

Evolution Of Sperm Activation In Nematodes, Qing Wei

Graduate School of Biomedical Sciences Theses and Dissertations

Three hermaphroditic species in the nematode genus Caenorhabditis - C. elegans, C. briggsae and C. tropicalis evolved independently from a male/female ancestor. Thus, the hermaphroditic reproductive system provides an ideal subject for studying the origin of new complex traits. Previous studies implied that this transition required two steps: a mutation that caused XY animals to make sperm, and a mutation that allowed XX spermatids to activate and fertilize oocytes. In this dissertation, I show how sperm activation is regulated in different hermaphroditic species.

First, I used TALENs to create genetic tools for C. briggsae and C. tropicalis. These tools were …

Efficient In Vitro Development Of Photoreceptors From Human Pluripotent Stem Cells, Joseph C. Reynolds

Dissertations, Masters Theses, Capstones, and Culminating Projects

Degeneration of the rod and cone photoreceptors in the human retina is among the most common causes of blindness. Replacing these damaged photoreceptors may help to restore vision. Repairing the damaged retina relies on the insertion of new, healthy cells. Embryonic stem (ES) cells and induced pluripotent stem (iPS) cells are two possible sources of photoreceptors to restore vision. Previous data shows that human ES cells and iPS cells can be differentiated into photoreceptors and transplanted into the eye to restore some vision. However, this process is inefficient, and costly. Here, we show a new method for inducing photoreceptor production …

The Development Of Skeletal Muscle In Young Horses: An Ultrasonography And Satellite Cell Approach, Emma K. Lavigne

Honors Scholar Theses

Muscle growth in young horses is characterized by an increase in muscle cross-sectional area, which can be accomplished through the activation and differentiation of satellite cells. Satellite cells can be stimulated or inhibited in response to different cytokines and growth factors and are key mediators of muscle hypertrophy and regeneration. The aim of this study was to investigate the growth of the longissimus dorsi (LD) muscle in horses under 5 years of age and to obtain preliminary data on satellite cell behavior in foals. The area, width, height, and subcutaneous fat were measured using ultrasonography at 6-month increments over the …

Effects Of Pre-Release Physical Stressors On Post-Release Success Of Hatchery-Reared Spotted Seatrout, Taylor Westbrook Guest

Master's Theses

Alteration of habitat associated with coastal development and increased demand for food and recreation can result in the depletion of fisheries resources such as the Spotted Seatrout (Cynoscion nebulosus), the Gulf of Mexico’s most popular recreational fish. Stock enhancement, or the release of cultured fish to supplement wild populations, is one potential tool for managing important fisheries resources. Although much effort has gone into marine stock enhancement, the effectiveness of stocking is not well established, and techniques for ensuring success have not been developed. Although the basic biology of the Spotted Seatrout is well known, comparatively little is known about …

Multilevel Deregulation Of Survival Mechanisms In Npm-Alk+ T-Cell Lymphoma, Deeksha Vishwamitra

Dissertations and Theses (Open Access)

The anaplastic lymphoma kinase (ALK) is a single chain transmembrane receptor tyrosine kinase that belongs to the insulin receptor superfamily. Other members of this superfamily include the insulin receptor (IR), type I insulin-like growth factor receptor (IGF-IR), and the leukocyte tyrosine kinase. The common structural finding among these tyrosine kinases is the YXXXYY motif present within their respective tyrosine kinase domains. Binding of its ligands causes ALK receptor homodimerization and protein kinase activation. ALK has been previously shown to play a significant role during early developmental stages. In human embryos, the expression of ALK is mainly seen in …

Pathological Effects Of Repeated Concussive Tbi In Mouse Models: Periventricular Damage And Ventriculomegaly, Richard H. Wolferz Jr.

Honors Scholar Theses

Repeated concussive traumatic brain injury (rcTBI) is the most prominent form of head injury affecting the brain, with an estimated 1.7 million Americans affected each year (Kuhn 2012). Neurologists have been concerned about the danger of repeated head impacts since the 1920’s, but researchers have only begun to understand the long-term effects of rcTBI (McKee 2009). Although symptoms can be as mild as dizziness, current research suggests that multiple concussions can lead to a progressive degenerative brain disease known as chronic traumatic encephalopathy (CTE) (Luo 2008, McKee 2009, Kane 2013). Research on the brain is just beginning to scratch the …

Developing A Catalog Of Socio-Sexual Behaviors Of Beluga Whales ( Delphinapterus Leucas ) In The Care Of Humans, Heather M. Hill, Sarah Dietrich, Deirdre Yeater, Mariyah Mckinnon, Malin Miller, Steve Aibel, Al Dove

Psychology Faculty Publications

The repertoire of socio-sexual and sexual behaviors of cetaceans is relatively unknown. The purpose of the current study was to advance the existing knowledge of socio-sexual behavior of beluga whales through the development of a behavioral catalog that lists the full repertoire of sexual and socio-sexual behaviors. A behavioral catalog was developed initially from 800 hours of observations, collected across a 7-year period from 11 belugas ranging in age (birth to 30+ years), sex, and social groupings. Using this behavioral catalog, observations of eight additional belugas housed between two other facilities were coded for socio-sexual and sexual behaviors. Socio-sexual and …

The Effect Of Red Maple Leaf Toxicosis On Reduced Glutathione Levels In Equine Erythrocytes In Vitro, Madeline A. Rohl

Undergraduate Honors Thesis Projects

Red maple leaf toxicosis is an equine blood disorder resulting from the consumption of wilted red maple (Acer rubrum L.) leaves by horses. Compounds within the leaves of red maple have oxidative effects on equine erythrocytes and can cause hemolysis of erythrocytes, the conversion of hemoglobin to methemoglobin, and the production of Heinz bodies. Reduced glutathione is important in the protection of equine erythrocytes from these oxidative events; however, in the presence of red maple toxin, glutathione is rapidly oxidized and is unavailable. The objective of this study is to determine whether the presence of vitamin C alters levels …

Microbial Communities Of The Providence River, Jacqueline Kratch

Honors Projects in Science and Technology

The Providence River has been industrialized for over one-hundred years. Industries such as oil storage and metal recycling facilities have left high levels of pollutant metals, including lead (Pb), in the soil and water. The elevated Pb concentrations in these environments influence the selection of Pb resistance mechanisms in the bacterial community1. One mechanism of heavy metal resistance is the Pb efflux pump, consisting of proteins in the cell membrane that aid in the transport of Pb out of the cell2. In this study we investigated the co-occurrence of Pb efflux pumps and antibiotic efflux pumps in bacteria from Pb …

Use And Misuse Of Material Transfer Agreements: Lessons In Proportionality From Research, Repositories, And Litigation, Tania M. Bubela, Jenilee Guebert, Amrita Mishra

Office of the Provost

Material transfer agreements exist to facilitate the exchange of materials and associated data between researchers as well as to protect the interests of the researchers and their institutions. But this dual mandate can be a source of frustration for researchers, creating administrative burdens and slowing down collaborations. We argue here that in most cases in pre-competitive research, a simple agreement would suffice; the more complex agreements and mechanisms for their negotiation should be reserved for cases where the risks posed to the institution and the potential commercial value of the research reagents is high.

Genome Engineering To Create Dominant Alleles In Caenorhabditis Elegans Using Crispr-Cas9 Technology, Abrar Sulaimani

Graduate School of Biomedical Sciences Theses and Dissertations

Many investigators have being using CRISPR-Cas9 as a method of genome engineering because it is easy, accurate and fast. This technique has been used to modify the genomes of a wide variety of organisms, including the nematode Caenorhabditis elegans (C. elegans). The short life cycle and ease of introducing exogenous plasmids make C. elegans an ideal system for advancing this technique. My thesis had two aims that focused on developing methods to create dominant alleles in C. elegans. Genetic modifications like precise deletion and insertions into a locus of chromosome are technically challenging. Additionally, although there are several ways of …

Validating A Method For Measuring Protein Domain And Lipid Binding Interactions Using Luciferase Fusion Proteins, Dezaray E. Thoen

Honors Capstones

Capstone submitted as a graduation requirement for the BSU Honors Program.

The Significance Of Crispr/Cas9-Directed Cul3 Knockout On Human Colorectal Cancer Cells, Zoe A. Lautz

Departmental Honors Projects

Cancer, the second leading cause of death in the US, is caused by mutations in select genes that alter cellular function leading to uncontrolled proliferation. Understanding the specific genes that drive cancer can lead to the generation of novel cancer therapies. To identify novel genes that drive cancer in the colon (CRC), lungs, and ovaries in mice, Starr et al. employed a transposon-based insertional mutagenesis system. One of the genes identified, APC, is mutated in 70-80% of human CRCs. CUL3, suspected to be a general driver gene, was discovered in the lung cancer screen. CUL3 was analyzed for its role …